(C-219) Quality Evaluation of Previous Studies on Glucocorticoid Use and Risk of Site-Specific Cancers: A Systematic Review

Background: Glucocorticoids, widely prescribed for allergic, respiratory, and rheumatological diseases, have long been suspected of increasing cancer risk due to their immunosuppressive and metabolic properties. Randomized trials assessing this risk are difficult to conduct and may be unethical, leaving observational studies the best option to determine whether use of glucocorticoids impacts cancer development. However, these studies face significant methodological issues that may compromise the validity of their findings.

Objectives: To evaluate the methodological rigor of observational studies assessing glucocorticoid use and site-specific cancer risks.

Methods: We performed a systematic review of observational studies on glucocorticoids and cancer published until 27th Avril 2023, using PubMed, Web of Science, Embase or Cochrane Library. We assessed methodological issues, including unclear research questions, inappropriate exposure definitions, prevalent user bias, immortal-time bias, time-window bias, reverse causation, detection bias, confounding by indication, and inappropriate adjustment for time-varying covariates such as body mass index and surveillance factors.

Results: Of the 75 studies included (26 cohort, 20 case-control, 27 nested case-control, and 2 case-cohort studies), only 29 (39%) were designed to investigate exclusively the effect of glucocorticoids on cancer risk. 13 studies were excluded from the quality evaluation due to presenting multiple adjusted estimates in a single table without clear model specification. Among the 62 studies evaluated, less than half considered cumulative exposure, 89% included prevalent users, 47% were prone to immortal-time or time-window biases, 41% failed to account for cancer latency and did not apply appropriate lag-time periods, 35% were subject to confounding by indication, and 5% inadequately adjusted for time-varying covariates.

Conclusions: This systematic review of observational studies provided an overview of the existing literature on the effect of glucocorticoids on cancer risk. The high prevalence of study design and analysis limitations could explain the contradictory findings reported to date on the associations between the use of glucocorticoids and cancer risk. Our review highlights the need to apply robust study designs and analytical approaches to generate unbiased estimates of the potential effect of glucocorticoids on cancer incidence in future studies.